Pathogen-resistant mosquitoes?

A bacterium that infects insects may provide a biological method for stunting the spread of a range of devastating human diseases. The bacteria may protect their hosts against disease-causing pathogens by hiking up the insects' immune response, according to a study published online today (October 1) in Science.
Image: Wikimedia commons, US Department of Agriculture"I think the paper is quite exciting," linkurl:Scott O'Neill;http://profiles.bacs.uq.edu.au/Scott.O%27Neill.

By Jef Akst | October 1, 2009

A bacterium that infects insects may provide a biological method for stunting the spread of a range of devastating human diseases. The bacteria may protect their hosts against disease-causing pathogens by hiking up the insects' immune response, according to a study published online today (October 1) in Science.

Image: Wikimedia commons, US Department of Agriculture

"I think the paper is quite exciting," linkurl:Scott O'Neill;http://profiles.bacs.uq.edu.au/Scott.O%27Neill.html of the University of Queensland in Australia wrote in an email to The Scientist. "The work is very interesting in the context of future disease control."
The wMelPop, or "popcorn," strain of Wolbachia occurs naturally in Drosophila melanogaster and is known to significantly reduce longevity of the fly. Earlier this year, the bacterium was found to have a similar effect on the mosquito Aedes aegypti: When artificially infected with the strain, the mosquito's lifespan was cut in half. But until now, the genetics behind Wolbachia's effects have remained elusive.
Using microarrays and quantitative-PCR experiments, molecular geneticist and Wellcome trust research fellow linkurl:Steven Sinkins;http://www.medawar.ox.ac.uk/sinkins/ and his colleagues at the University of Oxford identified a large and widespread increase in the expression of immune-related genes in mosquitoes infected with popcorn Wolbachia. Furthermore, the elevated levels of gene expression were detectable both two and 15 days after the infection, suggesting that the effect was long-lived, and not a short pulse of immune response as previous studies had shown for other bacterial infections.
"It's certainly a surprise that they are inducing the immune system at this scale," Sinkins said. "This effect might be contributing to that lifespan shortening phenotype."
The infection also translated into protection against filarial nematodes -- the causative agent of human lymphatic filariasis, a tropical disease that can cause severe damage to the lymph system. After feeding the mosquitoes a blood meal rife with nematodes, Wolbachia-infected mosquitoes contracted 80% fewer infective worms than mosquitoes that were Wolbachia-free.
Mosquitoes infected with the popcorn strain of Wolbachia were similarly protected against a virulent strain of a Gram-negative bacterium, suggesting this Wolbachia strain may protect mosquitoes against a broad range of pathogens, O'Neill said.
"It will be particularly interesting to see if Wolbachia infections can interfere with mosquito transmission of the major human pathogens like Plasmodium" -- the causative agent of malaria -- "and dengue viruses," O'Neill added. Indeed, some of the genes that were up-regulated in the Wolbachia-infected mosquitoes are known to inhibit the development of malaria-causing Plasmodium, hinting at this possibility. (linkurl:A feature in this month's issue;http://www.the-scientist.com/2009/10/1/44/1/ of The Scientist explores Wolbachia and other biological control agents for malaria in detail.)
But before Wolbachia can be used to control such diseases, "quite a few steps need to be covered first," warned evolutionary biologist linkurl:Ary Hoffmann;http://www.genetics.unimelb.edu.au/person/academics/ah.html of the University of Melbourne in an email. For one, "Ae. Aegypti is not a [natural] vector [of lymphatic filariasis], so the equivalent effects need to be demonstrated in vector species. Also it is not yet clear if wMelPop will spread in natural populations easily."
"Creating a stable infection of Wolbachia in mosquito species is quite a difficult thing to do," Sinkins admitted. For the popcorn Wolbachia to infiltrate a natural population of mosquitoes -- and therefore serve as an effective biological control agent for mosquito-borne diseases -- the strain must spread quickly, without causing too much harm to their insect hosts. A unique method that Wolbachia uses to promote its own survival may be key to making this system work, Hoffmann said. Because the bacterium is maternally transmitted, it can increase its spread by inferring a reproductive advantage to the females it infects -- a strategy known as cytoplasmic incompatibility (CI). "If there was no CI but negative host effects, the Wolbachia would quickly be lost," he said.
"If this particular Wolbachia strain can be shown to be capable of invading natural field populations of mosquito disease vectors," O'Neill said, "then it would suggest that the Wolbachia might have a major impact on disease transmission."
**__Related stories:__***linkurl:Evolution, Resisted;http://www.the-scientist.com/2009/10/1/44/1/ [October 2009]*linkurl:Anti-malaria genes give mosquitoes an edge;http://www.the-scientist.com/news/display/52945/ [20th March 2007]*linkurl:Mosquito virus spreading;http://www.the-scientist.com/news/display/23145/ [24th February 2006]